An electron paramagnetic resonance (EPR)- based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min. Three-dimensional maps of pH were reconstructed by processing the pH-dependent spectral information on the images. To demonstrate the proposed method of pH mapping, the progress of extracellular acidosis in tumor-bearing mouse legs was studied. Furthermore, extracellular pH mapping was used to visualize the spatial distribution of acidification in different tumor xenograft mouse models of human-derived pancreatic ductal adenocarcinoma cells. The proposed EPR-based pH mapping method enabled quantitative visualization of regional changes in extracellular pH associated with altered tumor metabolism.
Digital Commons Citation
Komarov, Denis A.; Ichikawa, Yuki; Yamamoto, Kumiko; Stewart, Neil J.; Matsumoto, Shingo; Yasui, Hironobu; Kirilyuk, Igor A.; Khramtsov, Valery V.; Inanami, Osamu; and Hirata, Hiroshi, "In Vivo Extracellular pH Mapping of Tumors Using Electron Paramagnetic Resonance" (2018). Clinical and Translational Science Institute. 30.
Komarov DA, Ichikawa Y, Yamamoto K, et al. In Vivo Extracellular pH Mapping of Tumors Using Electron Paramagnetic Resonance. Analytical Chemistry. 2018;90(23):13938-13945. doi:10.1021/acs.analchem.8b03328